The opioid epidemic continues to be one of the most consequential crises facing the United States. In 2019 alone, 70% of the nearly 71,000 drug overdose deaths involved an opioid. These numbers have been exacerbated due to the COVID-19 pandemic, which has caused millions of people to turn to drugs or alcohol to cope. Opioids also serve a very important role for those with chronic pain, oftentimes providing the only relief from pain that person can get. However, these drugs carry an immense potential for addiction, abuse, overdose, and death. Finding proper opioid alternatives that can not only treat chronic pain but also avoid the potential negative consequences such as addiction and overdose remains the most important front in the battle against opioid overdoses.
The Problem with Opioids for Chronic Pain
The major issue with opioids is how they interact with the brain. The receptors in the brain that react to opioids are not just pain receptors, they also act on regions of the brain that mediate breathing and reward. This means that opioids are not only addictive, but they can cause a blockade of breathing circuits, which can oftentimes be lethal.
Along with the potentially lethal side effects, opioids can also cause many other negative effects on the body. These can include constipation, nausea, and mental clouding, all of which can make life with chronic pain even more difficult.
In addition, long-term opioid use can also result in physical dependence, making it difficult to discontinue use even when the original cause of pain is no longer present. Furthermore, there is mounting evidence that long-term opioid use for pain can produce a chronic pain state, whereby patients find themselves in a vicious cycle, where opioids are used to treat pain caused by previous opioid use.
It’s these negative effects and the immense potential for abuse that have led the discussion surrounding opioid alternatives. One surprising alternative to opioids has recently been discovered by researchers at Harvard University and was a surprise to even those involved with the study.
How Anthrax Could be Used to Help Treat Chronic Pain
Researchers at Harvard Medical School have repurposed anthrax, a bacterial toxin known for its lethal effects, into a potent pain blocker that could someday become an alternative to drugs with addictive side effects such as opioids. Alternatives to opioids have been studied in the past, however, none have attempted to introduce a deadly toxin into the body to treat pain.
The study, published in the journal Nature Neuroscience, was headed by Associate Professor of Immunology Isaac Chiu of Harvard University. Chiu and his colleagues found that injecting anthrax toxin into the nervous system selectively quieted pain fibers and provided a novel way to target pain.
“Many of the conditions that cause chronic pain are very hard to treat, so we need to develop new ways of targeting pain circuits in the brain as well as in the body’s periphery,” Chiu said. “We were looking at what microbe-related genes pain fibers expressed that other neurons don’t, and one gene stood out, which is the receptor for anthrax toxin. It was not like we were looking for anthrax receptors, but that’s the one that popped out.”
So, how did Chiu and his team come to find anthrax as a possible opioid alternative? Let’s take a look.
How Does It Work?
As part of the team’s study, Chiu and his colleagues ran experiments to detect gene expression in mouse and human sensory nerves in the dorsal root ganglia (DRG). They found that these pain fibers had anthrax toxin receptor 2, which was not present in other central nervous system neurons.
Anthrax bacteria produce three proteins: protective antigen (PA), edema factor (EF), and lethal factor (LF). PA and EF together are referred to as “edema toxin” (ET).
Researchers then administered either anthrax LF or ET to the DRG of culture samples to observe the changes within cells. After confirming the effects of anthrax toxin in these samples, the researchers then conducted experiments in mice to explore the impact on pain sensation. Mice received injections of LF and EF with and without PA via the spinal canal.
They found that mice that were injected with ET had a decreased ability to sense heat, cold, and pinpricks without affecting their heart rate, body temperature, or motor functions. Additionally, the ET treatment did not cause cell death (apoptosis) in DRG samples or in mice who received the treatment.
The next step was to inject the ET solution into mice with simulated inflammation or neuropathic pain. The researchers found that ET reduced neuropathic and inflammatory pain responses in mice.
One of the things that struck Chiu and his colleagues was how anthrax interacts with the pain receptors in the brain. The receptors that interact with anthrax are known as high-affinity receptors. These receptors are also found in pain fibers but are absent in the brain or spinal cord neurons.
“That’s why anthrax is lethal in humans: it will target blood vessels, it will target the liver,” he explained. “But in our study, we were able to largely limit it to pain fibers by injecting the toxin only into the nervous system, between the vertebrae in the spine.”
Opioid alternatives such as this could pave the way for future chronic pain treatment, however, it is a long way from human trials.
Current Opioid Alternatives for Chronic Pain
Currently, chronic pain affects nearly 50 million Americans each year. Chiu says that while opioids can provide effective pain relief, the problem is their off-target effects, such as their addictive properties.
“The opioid crisis is still a major problem and finding solutions to develop non-opioid analgesics is a top priority of the National Institutes of Health,” he added.
It is these off-target effects that make opioid alternatives the single most important way to overcome the current opioid crisis. However, treatments like the one Chiu and his team are working on are far from human trials, and may take years to reach that point. So, what non-opioid treatments are there for chronic pain?
There are several opioid alternatives to help treat chronic pain. These can include medications available over the counter such as ibuprofen or acetaminophen, to nondrug therapies to help improve mobility and strengthen muscles. Some of these opioid alternatives may include:
- Physical Therapy: A physical therapist or physician who specializes in physical medicine and rehabilitation may be able to create an exercise program that helps you improve your ability to function and decreases your pain.
- Acupuncture: Acupuncture may not be for everyone, but you may find that it provides relief from chronic pain. This therapy involves very thin needles that are inserted at different places in your skin to interrupt pain signals.
- Surgery: Depending on the severity of your pain, what condition you’re living with, and what your doctor recommends, surgery may be a viable alternative to opioids. Surgery can help correct abnormalities within your body that may be causing your pain. As with any procedure, there are risks involved with surgery. It’s always important to talk with your doctor to see if surgery is right for you.
- Injections, Nerve Blocks, or Other Nonopioid Medicines: If you are having a muscle spasm or nerve pain, injections with local anesthetics or other medications can help short-circuit your pain. Other nonopioid medications may include acetaminophen, aspirin, and nonsteroidal anti-inflammatory drugs (NSAIDs).
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